title: Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE-/- mice.
abstract: Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease. The perivascular adipose tissue is closely implicated in the development of atherosclerosis; however, the contribution to CKD-associated atherogenesis remains undefined. Eight-week-old apoE-deficient mice were uninephrectomized and fed a high-cholesterol diet starting at 12 wk of age. The atherosclerotic lesion area in the thoracic aorta was comparable in 16-wk-old uninephrectomized (UNX) mice and sham control mice; however, the lesion area was markedly exaggerated in 20-wk-old UNX mice compared with the control (54%, P < 0.05). While the accumulation of monocytes/macrophages and the mRNA expression levels of inflammatory cytokines/chemokines in the thoracic periaortic adipose tissue (PAT) did not differ between the two groups, angiotensinogen (AGT) mRNA expression and the angiotensin II (ANG II) concentration in the PAT were significantly higher in 16-wk-old UNX mice than in the control (1.9- and 1.5-fold increases vs. control, respectively; P < 0.05). ANG II concentrations in both the plasma and epididymal white adipose tissue (WAT) were comparable between the two groups, suggesting that PAT-specific activation of the renin-angiotensin system (RAS) is primarily involved in CKD-associated atherogenesis. The homeostasis model assessment-insulin resistance (HOMA-IR) index and plasma insulin level after glucose loading were significantly elevated in 16-wk-old UNX mice. In vitro stimulation of preadipocytes with insulin exaggerated the AGT mRNA expression along with increased mRNA expression of PPARγ. These findings suggest that PAT-specific RAS activation probably primarily contributes in accelerating atherosclerotic development in UNX mice and could thus represent a therapeutic target for preventing CKD-associated atherogenesis.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; and.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawahito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Irie
authors.forename: Taku
authors.initials: T
authors.lastname: Kato
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akakabe
authors.forename: Sou
authors.initials: S
authors.lastname: Kishida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takata
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Wakana
authors.forename: Takehiro
authors.initials: T
authors.lastname: Ogata
authors.forename: Koji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ueyama
authors.forename: Satoaki
authors.initials: S
authors.lastname: Matoba
authors.forename: Yasukiyo
authors.initials: Y
authors.lastname: Mori
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004195:Disease Models, Animal; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy / Q000009:adverse effects*; D047495:PPAR gamma / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D007328:Insulin; D047495:PPAR gamma; D000808:Angiotensinogen; D000804:Angiotensin II
keywords: atherosclerosis; chronic kidney disease; periaortic adipose tissue; renin-angiotensin system